Method for assessing modulation of potassium ion channel activity

Abstract

The present invention relates to a method for assessing the ability of a compound to modulate the formation of a complex between a potassium channel and a protein tyrosine kinase. The method comprises the steps of (1) contacting a first polypeptide comprising the proline-rich binding region of the potassium channel, a second protein comprising the SH3 binding domain of the protein tyrosine kinase and the compound to be assessed; and (2) measuring the extent of complex formation between the first polypeptide and the second polypeptide.

We claim: 
     
       1. A method for determining if a compound modulates the binding of a potassium ion channel to the SH3 domain of a protein tyrosine kinase, wherein said potassium ion channel binds to said protein tyrosine kinase, comprising the steps of: (a) contacting the potassium ion channel with a polypeptide comprising the SH3 domain of the protein tyrosine kinase;   (b) contacting the potassium ion channel with the compound to be assessed; and   (c) measuring the extent of binding of the potassium ion channel and polypeptide comprising the SH3 domain of the protein tyrosine kinase wherein if the extent of binding is greater or less in the presence of the compound than the extent of binding in the absence of the compound, the compound modulates the binding of a potassium ion channel to the SH3 domain of a protein tyrosine kinase.     
     
     
       2. The method of claim 1 wherein the potassium ion channel is selected from the group consisting of Kv1.2, Kv1.3, Kv1.6, Kv3.1, Kv3.4, Kv4.1 and Kv4.3. 
     
     
       3. The method of claim 1 wherein the polypeptide comprises the SH3 domain of Src. 
     
     
       4. The method of claim 3 wherein the polypeptide is Src. 
     
     
       5. The method of claim 1 wherein the extent of binding of the potassium ion channel and the polypeptide comprising the SH3 domain of a protein tyrosine kinase is measured by co-immunoprecipitation or a two-hybrid system assay. 
     
     
       6. The method of claim 1 wherein the potassium ion channel is Kv1.5 and the protein tyrosine kinase is Src.